Backcrosses and intercrosses between recombinant-inbred and progenitor strains of mice confirmed that bone marrow-derived precursors of antibody-forming cells (B cells), suppressor T cells, and amplifier T cells participating in the antibody response to Type III pneumococcal polysaccharide (SSS-III) are under multigenic control. The genes involved act in a complimentary manner and are not linked to the major (H-2) histocompatibility complex or to the IgCH allotype complex. Congenic resistant strains of mice, selected for known genetic differences within the H-2 genetic complex, were found to differ significantly in their capacity to give an antibody response to SSS-III; this suggests that such strains may differ at other unselected genetic loci, including those involved in determining non-H-2-associated antibody responses to SSS-III and perhaps other antigens.